Glutamate-gated chloride channel (parasite) (GluCl)

Glutamate-gated chloride channels (GluCl) are pentameric ligand-gated ion channels found exclusively in protostome invertebrates, such as nematodes, arthropods, and certain mollusks and flatworms. Each channel consists of five subunits, each with an N-terminal extracellular ligand-binding domain (for glutamate) and four transmembrane helices. Upon glutamate binding, the channel opens to allow chloride ion influx, resulting in neuronal hyperpolarization and inhibition of excitability. GluCl channels are the principal molecular targets for macrocyclic lactone anthelmintics (such as ivermectin), which act as potent agonists and allosteric modulators by binding within the transmembrane region and causing persistent channel opening. The resulting paralysis and death of the parasite make GluCl a critical target for both veterinary and human antiparasitic therapies. GluCl is absent in vertebrates, contributing to the selectivity and safety of the drugs, although resistance and rare toxicity are ongoing challenges.

Other names

GluCl channelGluCl receptorIvermectin-sensitive chloride channel

Positive allosteric modulation and agonism: macrocyclic lactones (e.g., ivermectin) bind GluCl and cause persistent opening of the chloride channel, leading to sustained chloride influx, hyperpolarization of neuronal or muscle membranes, paralysis, and death of the parasite.